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Explaining the link between adiposity and colorectal cancer risk in men and postmenopausal women in the UK Biobank: A sequential causal mediation analysis
Author(s) -
Dashti S. Ghazaleh,
Viallon Vivian,
Simpson Julie A.,
Karahalios Amalia,
MorenoBetancur Margarita,
English Dallas R.,
Gunter Marc J.,
Murphy Neil
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32980
Subject(s) - medicine , waist , body mass index , sex hormone binding globulin , endocrinology , obesity , confidence interval , testosterone (patch) , metabolic syndrome , hormone , androgen
Mechanisms underlying adiposity–colorectal cancer (CRC) association are incompletely understood. Using UK Biobank data, we investigated the role of C‐reactive protein (CRP), hemoglobin‐A1c (HbA1c) and (jointly) sex hormone‐binding globulin (SHBG) and testosterone, in explaining this association. Total effect of obesity versus normal‐weight (based on waist circumference, body mass index, waist–hip ratio) on CRC risk was decomposed into natural direct (NDE) and indirect (NIE) effects using sequential mediation analysis. After a median follow‐up of 7.1 years, 2070 incident CRC cases (men = 1,280; postmenopausal women = 790) were recorded. For men, the adjusted risk ratio (RR) for waist circumference (≥102 vs . ≤94 cm) was 1.37 (95% confidence interval [CI], 1.19–1.58). The RRs NIE were 1.08 (95% CI: 1.01–1.16) through all biomarkers, 1.06 (95% CI: 1.01–1.11) through pathways influenced by CRP, 0.99 (95% CI: 0.97–1.01) through HbA1c beyond (the potential influence of) CRP and 1.03 (95% CI: 0.99–1.08) through SHBG and testosterone combined beyond CRP and HbA1c. The RR NDE was 1.26 (95% CI: 1.09–1.47). For women, the RR for waist circumference (≥88 vs . ≤80 cm) was 1.27 (95% CI: 1.07–1.50). The RRs NIE were 1.08 (95% CI: 0.94–1.22) through all biomarkers, 1.08 (95% CI: 0.99–1.17) through CRP, 1.00 (95% CI: 0.98–1.02) through HbA1c beyond CRP and 1.00 (95% CI: 0.92–1.09) through SHBG and testosterone combined beyond CRP and HbA1c. The RR NDE was 1.18 (95% CI: 0.96–1.45). For men and women, pathways influenced by CRP explained a small proportion of the adiposity‐CRC association. Testosterone and SHBG also explained a small proportion of this association in men. These results suggest that pathways marked by these obesity‐related factors may not explain a large proportion of the adiposity‐CRC association.